Calcium release activated calcium (CRAC) channels are a subset of store operated channels (SOC) which are opened in response to depletion of intracellular calcium stores and represent the critical point of calcium entry into certain cells such as mast cells and T-cells.
Two proteins have been identified as the essential components for CRAC channel function namely STIM1 (stromal interaction molecule 1), a calcium sensor localised in the endoplasmic reticulum, and ORAI1, a pore subunit of the CRAC channel that is gated by STIM1.
Small molecule inhibitors of the CRAC channel current (hereafter ICRAC inhibitors) are known in the art, their identification and therapeutic potential are described by Derler et al (Expert Opin. Drug Discovery; 2008; Vol. 3(7) pp. 787-800). U.S. Pat. No. 6,958,339 discloses a series of pyrazole derivatives that are said to possess calcium release-activated calcium channel inhibitory activity which are believed to be useful in the treatment of allergic, inflammatory or autoimmune diseases.
PCT patent application PCT/EP2010/055318 discloses a series of pyrazole amide compounds which are calcium release activated calcium channel (ICRAC) inhibitors.